Clinical Translational Core Project Summary / Abstract Major advances in our understanding of the genetic and environmental structure of neurodevelopmental disorders present new opportunities to prevent or ameliorate intellectual and developmental disabilities (IDD). The Clinical Translational Core (CTC) of the IDDRC@WUSTL will serve as an essential institutional resource for supporting research that applies scientific discoveries on pathogenic mechanisms of IDD to benefit actual patients through the development of high-impact personalized intervention that is guided by information generated from natural history studies, biomarker development, and clinical trials. The CTC will serve as an integrative scientific hub of the IDDRC@WUSTL linking patients along with their clinical and behavioral data to clinical studies in the CTC and to research opportunities with the Model Systems Core and the Developmental Neuroimaging Core. The Specific Aims of the CTC, designed to accelerate translational advances in IDD, are as follows: 1) To provide investigators with the expertise, resources, and assessment services needed to conduct comprehensive clinical, behavioral, and genomic characterization of human subjects for IDD-related research and clinical trials through the Human Genomic and Phenotypic Characterization Unit (HGPCU) and Clinical Trials Unit (CTU), and to leverage this activity with established, state-of-the-art genome technology services at WUSTL to contribute to understanding of the pathogenicity and functional significance of variation in genes influencing the developing human brain. 2) To strategically harness services and expertise of allied WUSTL facilities that critically and cost-effectively complement the IDDRC@WUSTL scientific cores to contribute to a discovery pipeline for higher-impact intervention and clinical trials for individuals affected by or at risk for IDD. Initial implications-for-treatment of new discoveries in IDD pathogenesis are often first discovered through advances in the Model Systems Core and made ready for translational applications utilizing CTC services. Similarly, brain circuitry data from the Developmental Neuroimaging Core are assimilated with behavioral and genomic data collected using CTC resources to identify early biomarker risk profiles and inform developmental timing of intervention and prevention, 3) To promote bidirectional interchange between scientific activity in the discovery of pathogenic mechanisms and the testing of novel approaches to IDD prevention and treatment in human subjects and among populations at risk. This will occur in the context of a dynamic interface with the other two scientific core facilities of the IDDRC@WUSTL (the Developmental Neuroimaging and Model Systems Cores), facilitated by dedicated faculty liaisons whose roles are to cultivate cross-disciplinary science.